Method of modifying the balance of omega unsaturated fatty acids using a dioxabicyclo octane derivative

ABSTRACT

The present invention discloses an omega-3/omega-6 unsaturated fatty acid balance modifying composition whose active ingredient is a dioxabicyclo(3.3.0)octane derivative represented with general formula (I): ##STR1## (wherein, R 1 , R 2 , R 3 , R 4 , R 5  and R 6  are respectively and independently a hydrogen atom or alkyl group having 1-3 carbon atoms, or R 1  and R 2  and/or R 4  and R 5  together represent a methylene group or ethylene group, and n, m and l represent 0 or 1).

TECHNICAL FIELD

The present invention relates to a food composition containing anomega-6/omega-3 unsaturated fatty acid balance modifier whose activeingredient is a dioxabicyclo(3.3.0)octane derivative, and to anomega-6/omega-3 unsaturated fatty acid balance modifier.

BACKGROUND ART

Since polyunsaturated fatty acids are essential fatty acids, the amountingested for satisfying the required amount from a nutritional viewpointhas been discussed. At present, however, since the ingested amount issufficient, attention has focused on serum lipid lowering effects,resulting in a situation in which emphasis is placed on the ratio ofunsaturated fatty acids to saturated fatty acids of ingested fats. Onthe other hand, there are two representatives series of unsaturatedfatty acids, namely omega-3 and omega-6 (omega indicates the number ofcarbon atoms from the terminal methyl group of the fatty acid to thecarbon atom at which the first double bond is located). Recently, agrowing emphasis has come to be placed on the ratio of these omega-6fatty acids to omega-3 fatty acids.

Although it has been confirmed that various fatty acids such as omega-6fatty acids, including linoleic acid, dihomo-γ-linolenic acid andarachidonic acid, and omega-3 fatty acids, including α-linolenic acid,eicosapentaenoic acid and docosahexaenoic acid, exhibit differentphysiological actions, at the same time, what is important is that thesetwo series of unsaturated fatty acids mutually have a potent effect onthe physiological action of the other, as well as that both of theseseries of fatty acids cannot be biosynthesized in the body, both seriesare not interchangeable, and the ratio of omega-3 and omega-6unsaturated fatty acids in the body reflects that in the diet.

In view of these circumstances, Japanese Unexamined Patent PublicationNo. 3-53869 discloses a food in which the fatty acid composition thereinis adjusted so that the ratio of omega-3 fatty acids to omega-6 fattyacids is 1:1 to 1:5. In the revision of Japanese nutritionalrequirements of 1994 (Japanese Ministry of Health and Welfare, 5thRevision of Japanese Nutritional Requirements, pp. 56-58, 1994), it isstated that the preferable ratio of omega-6 unsaturated fatty acids toomega-3 unsaturated fatty acids is 4:1. However, it is difficult duringthe daily life to ingest only foods in which the ratio of omega-6 andomega-3 fatty acids is adjusted, and is essentially difficult toconstantly keep in mind the ingestion ratio of omega-6 and omega-3unsaturated fatty acids.

In addition, since the Japanese diet has been Westernized recently,there has been a considerable increase in the opportunities to consumemeals made primarily of meat resulting in an increase in the ingestionof omega-6 fatty acids in comparison with omega-3 fatty acids. Due tothis trend, there has been a dramatic increase in the mortality rate dueto arteriosclerotic diseases such as myocardial infarction and cerebralthrombosis. In order to improve this situation, foods and nutritionalsupplements have been developed to which have been added omega-3unsaturated fatty acids such as eicosapentaenoic acid anddocosahexaenoic acid concentrated to high concentrations. However, inconsidering actual dietary habits, it is virtually impossible to consumeonly one type of fatty acid. In particular, it is dangerous to ingestlarge amount of only one of these types of unsaturated fatty acids inconsideration of the physiological functions of omega-3 and omega-6unsaturated fatty acids.

For instance, examples of metabolic disorders thought to occur due toingestion of large amounts of omega-6 unsaturated fatty acids include:(1) disturbance in the balance of eicosanoid production (promotion ofthrombus formation, arteriosclerosis and allergic reactions), (2)accelerated gallstone formation, (3) promotion of cancer cell growth(including breast cancer and colon cancer), and (4) depressed immunityand reduced phagocyte function. In addition, examples of metabolicdisorders thought to occur accompanying excessive ingestion of omega-3unsaturated fatty acids (and particularly fish oil containingeicosapentaenoic acid and docosahexaenoic acid) include: (1) myocardialnecrosis, (2) liver disorders and decreased liver function, (3)increased sensitivity to catecholamines, and (4) myocardial lipidosiscaused by long-chain monoenic acids, increased bleeding time, andgreater susceptibility to hemorrhaging and clotting difficulties due toreduced platelet levels.

As has been described above, when referring to unsaturated fatty acids,it is not appropriate to refer to omega-6 series or omega-3 series fattyacids alone. In order to maintain homeostasis of the body and preventdisease, the ingestion ratio of omega-6 and omega-3 series unsaturatedfatty acids among the unsaturated fatty acids ingested must be balanced.In addition, those omega-6 unsaturated fatty acids which can be obtainedfrom a normal diet mainly comprise linoleic acid, while the majority ofomega-3 unsaturated fatty acids are α-linolenic acid or eicosapentaenoicacid and docosahexaenoic acid from fish oil.

Since it is known that eicosapentaenoic acid and docosahexaenoic acidinhibit conversion from linoleic acid to dihomo-γ-linolenic acid andarachidonic acid (precursors of omega-6 eicosanoids), the balance ofthese unsaturated fatty acids has an effect on the fatty acidcomposition of the body, which effect is greater than their actualconsumption ratio. Thus, it is extremely difficult to determine theingestion ratio and its amounts in consideration of dynamics in thebody. Therefore, there was a strong desire to develop a safe substancethat suitably adjusts the ratio of omega-6 unsaturated fatty acids andomega-3 unsaturated fatty acids in the body in order to maintainhomeostasis of the body as well as prevent disease.

DISCLOSURE OF THE INVENTION

Thus, the present invention provides a food composition containing anomega-6/omega-3 unsaturated fatty acid balance modifier whose its activeingredient is a dioxabicyclo(3.3.0)octane derivative, and to anomega-6/omega-3 unsaturated fatty acid balance modifier.

As a result of various research to achieve the above-mentioned object ofthe present invention, the inventors of the present invention found thatdioxabicyclo(3.3.0)octane derivatives obtained by isolation from sesameseeds, sesame oil and by-products of the sesame oil manufacturingprocess or by synthesis have the effect of modifying the balance ofomega-6 and omega-3 unsaturated fatty acids while also having a highdegree of safety, thereby leading to completion of the presentinvention.

Thus, the present invention provides an omega-6/omega-3 unsaturatedfatty acid balance modifier, or a food composition containing saidmodifier, whose active ingredient is the dioxabicyclo(3.3.0)octanederivative, represented with the following general formula (I): ##STR2##(wherein, R¹, R², R³, R⁴, R⁵ and R⁶ are respectively and independently ahydrogen atom or alkyl group having 1 to 3 carbon atoms, or R¹ and R²and/or R⁴ and R⁵ together represent a methylene group or ethylene group,and n, m and l represent 0 or 1).

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a graph showing the proportions of omega-3 unsaturated fattyacid and omega-6 unsaturated fatty acid in the liver, lung, heart,kidney and brain of male Wistar rats fed with linoleic acid, α-linolenicacid or eicosapentaenoic acid with and without a mixture of sesamin andepisesamin.

FIG. 2 is a graph showing the proportions of omega-3 and omega-6unsaturated fatty acids in the liver, lung, heart, kidney and brain ofmale Wistar rats fed with linoleic acid or arachidonic acid with andwithout a mixture of sesamin and episesamin.

DETAILED EXPLANATION

The dioxabicyclo(3.3.0)octane derivatives that are the activeingredients of the present invention are a compound represented with thefollowing general formula (I): ##STR3## (wherein, R¹, R², R³, R⁴, R⁵ andR⁶ are respectively and independently a hydrogen atom or alkyl grouphaving 1 to 3 carbon atoms, or R¹ and R² and/or R⁴ and R⁵ togetherrepresent a methylene group or ethylene group, and n, m and l represent0 or 1). Here, examples of an alkyl group having 1 to 3 carbon atomsinclude a methyl group, ethyl group, n-propyl group and isopropyl group.

Moreover, specific examples of this compounds include sesamin,sesaminol, episesamin, episesaminol, sesamolin,2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane,2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane, and2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo(3.3.0)octane.These compounds may be in the form of glycosides, and optically activesubstances and isomers are also included in the invention of the presentapplication.

In the present invention, the above-mentioned dioxabicyclo(3.3.0)octanederivatives (to be referred to as the derivatives of the presentinvention) can be used alone or in a combination of two or more. Inaddition, in the present invention, the derivatives of the presentinvention are not limited to highly pure purification products, butrather substances can also be used that contain the derivatives of thepresent invention which are obtained from naturally-occurring substancesthat contain the derivative of the present invention as well assubstances obtained by isolation procedures such as water vapordistillation and molecular distillation (e.g. the methods described inJapanese Examined Patent Publication No. 7-25764 and Japanese UnexaminedPatent Publication No. 6-169784). Examples of naturally-occurringsubstances that contain the derivative of the present invention includesesame oil, by-products of the sesame oil manufacturing process (e.g.defatted dregs of sesame seeds and deodorized scum of sesame oil),sesame seeds, Gokahi, Toboku, Hakka Juhi, Hihutsu, Saishin or culturesobtained by culturing reproductive cells derived from sesame plant(Japanese Unexamined Patent Publication No. 63-207389).

In addition, the compound containing the derivatives of the presentinvention should contain at least 0.2 wt %, preferably at least 2.0 wt %and more preferably at least 10.0 wt % of the derivatives of the presentinvention, and more particularly, the total content of sesamin,episesamin, sesaminol, episesaminol and sesamolin should be at least 0.1wt %, preferably at least 1.0 wt % and more preferably at least 5.0 wt%.

For example, in order to obtain a product containing the derivatives ofthe present invention by extraction from sesame oil, it can be extractedand concentrated using various organic solvents that are substantiallyimmiscible with sesame oil and are able to extract and dissolve thederivative of the present invention (e.g. acetone, methylethyl ketone,diethyl ketone, methanol and ethanol). One example of a method forobtaining the product containing the derivative of the present inventioninvolves uniformly mixing sesame oil with any of the above-mentionedsolvents, allowing the mixture to stand undisturbed at a lowtemperature, performing phase separation in accordance with routinemethods such as centrifugal separation, and distilling off the solventfrom the solvent fraction. More specifically, after dissolving sesameoil in 2 to 10 volumes, and preferably 6 to 8 volumes, of acetone, thesolution is allowed to stand undisturbed overnight at -80° C., theresulting oil component forms a precipitate, and the acetone is removedfrom the filtrate obtained by filtration to obtain an extract having asits main ingredient the derivative of the present invention.

In addition, another method for obtaining a product containing thederivative of the present invention comprises mixing sesame oil with hotmethanol or hot ethanol, allowing the mixture to stand undisturbed atroom temperature and distilling off the solvent from the solventfraction. More specifically, after vigorously mixing sesame oil with 2to 10 volumes, and preferably 5 to 7 volumes, of hot methanol (50° C. orhigher) or hot ethanol (50° C. or higher), phase separation is carriedout in accordance with routine methods such as by standing the mixtureundisturbed at room temperature or by centrifugal separation, and thesolvent is distilled off from the solvent fraction to obtain an extracthaving for its main ingredient the derivative of the present invention.Moreover, the extract can also be obtained by utilizing super-criticalgas extraction. The sesame oil to be used may be a finished product orany of the crude products in the production process of sesame oil priorto the decoloring step.

In addition, in order to obtain a product containing the derivative ofthe present invention by extraction from sesame seeds or the defattedproducts sesame seeds (residual oil content: 8 to 10%), after crushingthe sesame seeds or defatted products as necessary, extraction can beperformed in accordance with routine methods using any solvent such asthe same solvents used in extraction from sesame oil as described above.After separating the extraction residue, the solvent is removed from theextract liquid by evaporation and so forth to obtain the extract.

To obtain the derivative of the present invention, the target compoundcan be isolated from a product containing the derivative of the presentinvention separated according to the methods described above, bytreating in accordance with routine methods such as columnchromatography, high-performance liquid chromatography,recrystallization, distillation and liquid-liquid exchange distributionchromatography.

More specifically, after fractionating the above-mentioned extract withhigh-performance liquid chromatography using a reverse phase column(5C₁₈) and methanol/water (60:40) for the eluent, and distilling off thesolvent, the resulting crystals are recrystallized with ethanol toobtain a derivative of the present invention such as sesamin, sesaminol,episesamin, episesaminol, sesamolin,2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane,2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane, and2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo(3.3.0)octane.Furthermore, the methods for obtaining and purifying the derivative ofthe present invention and products containing said derivative are notlimited to those described above.

In addition, the derivative of the present invention can also beobtained by synthesis in accordance with routine methods.

For example, sesamin and episesamin can be synthesized with the methodof Beroza et al. (J. Am. Chem. Soc. 78, 1242 (1956)), pinoresinol (R¹=R⁴ =H, R² =R⁵ =CH₃ and n=m=l=0 in general formula (I)) can besynthesized with the method of Freundenberg et al. (Chem. Ber., 86, 1157(1953)), and silingaresinol (R¹ =R⁴ =H, R² =R³ =R⁵ =R⁶ =CH₃, n=0 andm=l=1 in general formula (I)) can be synthesized with the method ofFreundenberg et al. (Chem. Ber., 88, 16 (1955)).

Moreover, the derivative of the present invention can be used incombination with an antioxidant. Examples of antioxidants includenatural antioxidants such as tocopherols, flavone derivatives,phyllodulcins, kojic acid, gallic acid derivatives, catechins, fukinolicacid, gossypol, pyrazine derivatives, sesamol, guaiacol, guaiac resin,p-coumalic acid, nordihydroguaiaretic acid, sterols, terpenes, nucleicacid bases and carotenoides, or synthetic antioxidants represented bybutylhydroxyanisol (BHA), butylhydroxytoluene (BHT),monotertiary-butylhydroquinone (TBHQ) and4-hydroxymethyl-2,6-di-tertiary-butylphenol (HMBP).

Among the above-mentioned antioxidants, tocopherols are preferable,examples of which include α-tocopherol, β-tocopherol, γ-tocopherol,δ-tocopherol, ε-tocopherol, ξ-tocopherol, η-tocopherol and tocopherolester (e.g. tocopherol acetate). Moreover, examples of carotenoidsinclude β-carotene, cantaxanthine and astaxanthine.

Although there are no particular restrictions on the blending ratio ofthe derivative of the present invention and antioxidant, 0.001 to 1000parts by weight of antioxidant per 1 part by weight of the derivative ofthe present invention is desirable. Moreover, a range of 0.01 to 100parts by weight is preferable, and a range of 0.1 to 100 parts by weightis more preferable.

In the present invention, "omega-6/omega-3 unsaturated fatty acidbalance" or simply "balance" refers to the ratio between omega-3unsaturated fatty acids and omega-6 unsaturated fatty acids in the body.For example, the ratio of omega-3 unsaturated fatty acids and omega-6unsaturated fatty acids in the liver or serum can be used as anindicator. Here, omega-3 unsaturated fatty acids refer to9,12,15-octadecatrienoic acid (also referred to as α-linolenic acid"LLA"), 6,9,12,15-octadecatetraenoic acid, 8,11,14,17-eicosatetraenoicacid, 5,8,11,14,17-eicosapentaenoic acid (also referred to as "EPA"),7,10,13,16,19-docosapentaenoic acid and 4,7,10,13,16,19-docosahexaenoicacid (also referred to as "DHA"), while omega-6 unsaturated fatty acidsrefer to 9,12-octadecadienoic acid (linoleic acid),6,9,12,-octadecatrienoic acid (also referred to as γ-linolenic acid,"GLA"), 8,11,14-eicosatrienoic acid (also referred to asdihomo-γ-linolenic acid, "DGLA") and 5,8,11,14-eicosatetraenoic acid(also referred to as arachidonic acid, "AA").

In addition, "balance modification" refers to the action of recoveringthe balance destroyed by excessive ingestion of omega-3 unsaturatedfatty acids or omega-6 unsaturated fatty acids to the normal balance tobe inherently maintained in the body. The normal balance to beinherently maintained in the body refers to the balance of omega-3unsaturated fatty acids and omega-6 unsaturated fatty acids in the bodywhen omega-6 unsaturated fatty acids (n-6) and omega-3 unsaturated fattyacids (n-3) are ingested in a ratio of n-6/n-3=1 to 5 and preferably 2to 4. For example, the balance in the liver is n-6/n-3=1 to 6 andpreferably 2 to 5. However, this balance is not always limited to thesevalues due to the presence of individual differences.

This balance modification is thought to be performed by lowering thelevel of omega-3 unsaturated fatty acids that has risen above the normalvalue and raising the level of omega-6 unsaturated fatty acids thatfallen below the normal value due to ingestion of a diet or health foodsand so forth rich in omega-3 unsaturated fatty acids. In addition, thisbalance modification is thought to be performed by significantlylowering the level of omega-6 unsaturated fatty acids that have risenabove the normal value and inhibiting the significant decrease in thelevel of omega-3 unsaturated fatty acids below the normal value due toingestion of a diet or health foods and so forth rich in omega-6unsaturated fatty acids. The modifying action produced by the activeingredient of the present invention is demonstrated more effectivelywhen the final products in the body, such as EPA and DHA or DGLA and AA,are ingested in excess.

Thus, the balance modifier or food composition of the present inventionis more effective in persons consuming a diet rich in fish or meat, andpersons consuming foods laden with omega-3 unsaturated fatty acidsand/or omega-6 unsaturated fatty acids. When consumption of fish or meattends to be regularly unbalanced, the balance modifier or foodcomposition of the present invention can be taken or ingested before,after or during meals. In addition, in the case of health foods rich inomega-3 unsaturated fatty acids or omega-6 unsaturated fatty acids, thebalance modifier of the present invention can be added to said healthfoods or the balance modifier or food composition of the presentinvention can be used in combination with said health foods.

For example, although soft capsules comprising oil containing EPA andDHA obtained by purification of fish oil are sold as EPA products, theactive ingredient of the present invention can be contained to said EPAproduct or soft capsules containing the active ingredient of the presentinvention can be ingested with said EPA product to inhibit thedetrimental effects on the body caused by excessive ingestion of EPA. Inaddition, although prepared powdered milk containing fish oil has beenplaced on the market in recent years for the purpose of adding DHA, theomega-6/omega-3 unsaturated fatty acid balance modifier of the presentinvention can be contained to said prepared powdered milk.

In the case of using the derivative of the present invention as apharmaceutical, any type of formulation may be used provided oraladministration or parenteral administration can be performed easily,examples of which include injections, infusions, powders, granules,tablets, capsules, enteric coated pills, troches, liquid for internaluse, suspensions, emulsions, syrups, liquid for external use,fomentations, nasal drops, ear drops, eye drops, inhalants, ointments,lotions, suppositories and transintestinal nutrient preparations. Thesecan be used either alone or in combination according to symptoms.

Each of these preparations can be formulated using known adjuvants thatcan be conventionally used in the field of pharmaceutical preparationtechnology, such as a vehicle, binder, antiseptic, stabilizer,disintegration agent, lubricator or corrective, with the primary drugaccording to the purpose of administration in accordance with routinemethods. For example, in the case of preparing an injection, asolubilizer for pharmaceutical products such as a non-ionic surfaceactivator can be used. More specifically, a preparation can be preparedby heating and dissolving the derivative of the present invention in 80volumes of a non-ionic surfactant such as POE(60) cured castor oil orPOE sorbitan monooleate followed by diluting with physiological saline.In addition, an isotonic agent, stabilizer, antiseptic or analgesic maybe suitably added as necessary.

In addition, in the case of external preparations, ointments, creams andso forth can be prepared according to routine methods using vaseline,paraffin, fat and oils, lanolin, macrogol and so forth for the base. Inaddition, although the dose varies according to the purpose ofadministration and status of the patient (sex, age, body weight, etc.),the normal adult dose in the case of oral administration in terms of thetotal amount of derivative of the present invention is 1 mg to 10 g perday, preferably 1 mg to 2 g per day, and more preferably 1 mg to 200 mgper day, while in the case of parenteral administration, the dose is 0.1mg to 1 g per day, preferably 0.1 mg to 200 mg per day, and morepreferably 0.1 mg to 100 mg per day, all of which can be suitablyadjusted.

In addition, since the omega-6/omega-3 unsaturated fatty acid balancemodifying action of the derivative of the present invention is enhancedby administration with antioxidant, and particularly tocopherols,although varying according to the purpose of administration and statusof the patient (sex, age, body weight, etc.), the normal adult dose ofthe derivative of the present invention in the case of oraladministration in terms of the total amount of derivative of the presentinvention is 0.1 mg to 2 g per day, preferably 0.1 mg to 500 mg per day,and more preferably 0.1 mg to 100 mg per day, while in the case ofparenteral administration, the dose is 0.01 mg to 200 mg per day,preferably 0.01 to 50 mg per day, and more preferably 0.01 to 20 mg perday. Moreover, the blending ratio of the derivative of the presentinvention and antioxidant is 0.001 to 1000 parts by weight, preferably0.01 to 100 parts by weight, and more preferably 0.1 to 100 parts byweight of antioxidant per 1 part by weight of the derivative of thepresent invention, all of which can be suitably adjusted.

Since the derivatives of the present invention are compounds found inconventional foods or similar compounds, it is clear that they aresuperior in terms of safety. In addition, when sesamin was administereddaily for 2 weeks (oral administration) at 2.14 g/day/kg to 7 week old,male IRC mice, there were no abnormalities observed, thereby confirmingthe above-mentioned safety.

Examples of food compositions containing the balance modifier of thepresent invention include general foods, functional foods, nutritionalsupplements, premature infant formula, infant formula, baby food,pregnancy foods and geriatric foods.

Although there are no particular restrictions on the food form, the foodcomposition may be in the form of powdered or liquid premature infant orinfant formula, ordinary solid or liquid foods, or foods containingoils. Examples of foods containing oils include natural foods containingoils such as meat, fish or nut, foods to which oils are added duringpreparation such as Chinese food, Chinese noodles and soups, foodsprepared using oils as a heat medium such as tempura, fried fish, friedbean curd, fried rice, doughnuts and fried confections, oily foods orprocessed foods to which oils are added during processing such asbutter, margarine, mayonnaise, salad dressing, chocolate, instantChinese noodles, caramel, cookies and ice cream, and foods that aresprayed or coated with oils during final processing such as ricecrackers, soda crackers and breads.

However, these examples are not limited to foods containing oils, butalso include agricultural foods such as bread, noodles, rice,confections, bean curd and their processed foods, fermented foods suchas rice wine and pharmaceutical alcoholic beverages, dairy products suchas sweet rice wine, vinegar, soy sauce, fermented bean paste, saladdressing, yogurt, ham, bacon, sausage and mayonnaise, marine foods suchas pressed fish, deep-fried shrimp and fish cake, and beverages such asfruit juice, soft drinks, sports drinks, alcoholic beverages and tea.

In addition, in the case of using the balance modifier of the presentinvention as a health food, functional food or nutritional supplementand so forth, the form used may be the form of the above-mentionedpharmaceuticals or foods and drinks, examples of which include a mixtureof the active ingredient of the present invention with vegetable oil,fish oil or microbial oil (e.g. microbial oil containing EPA and/or DHA,microbial oil containing GLA or microbial oil containing DGLA and/or AA)that is encapsulated, powdered or granulated, a processed foods such asnatural liquid foods; semi-digested nutritional foods; componentnutritional foods containing proteins (although proteins such as milkprotein, soy bean protein and egg albumin having balanced amino acidsand high nutritional value are commonly used for the protein source,their degradation products, egg white oligopeptides, soy beanhydrolysates as well as mixtures of individual amino acids are alsoused), sugars, fats, trace elements, vitamins, emulsions and perfumes;drinks or transintestinal nutrient preparations.

In addition, while the food composition of the present invention can beused in healthy persons, it can also be used, for example, in the formof meals to which the balance modifier of the present invention has beenadded under the supervision of a nutritionist based on the instructionsof a physician.

The food composition of the present invention can be processed andmanufactured according to routine manufacturing methods using thebalance modifier of the present invention and the food raw material (andparticularly a raw material that does not substantially contain theactive ingredient of the present invention). Although varying accordingto the properties of the drug form or food form, the content of thebalance modifier of the present invention is typically at least 0.001%,preferably at least 1.4%, and more preferably at least 2%, althoughthere are no particular limitations.

In the present invention, although examples of food raw materials notsubstantially containing the active ingredient of the present inventioninclude food raw materials other than, for example, sesame, even ifsesame is used as the food raw material, foods in which the amount ofeffective ingredient of the present invention contained in the finishedproduct is extremely low and the total content of the active ingredientof the present invention is less than 0.1 mg, and preferably 0.8 mg orless, per amount of that product ingested per day, and foods in whichthe total content of sesamin, sesaminol, episesamin, episesaminol,sesamolin,2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane,2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0) octane, and2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo(3.3.0)octaneis less than 0.1 mg, and preferably 0.8 mg or less, per amount of thatproduct ingested per day are included in food raw materials that do notsubstantially contain the derivative of the present invention.

It is desirable to orally ingest the food composition of the presentinvention in an amount of 1 mg to 10 g, preferably 1 mg to 2 g and morepreferably 1 mg to 200 mg per day in terms of the total amount of thederivative of the present invention for the purpose of adjusting thebalance of omega-6 and omega-3 unsaturated fatty acids to the normalvalue after it has broken down due to an unbalanced diet.

Moreover, in the food composition of the present invention, in the casethe balance modifier of the present invention has for its activeingredient the derivative of the present invention and an antioxidant,it is preferable that said food composition be orally ingested in anamount of 0.1 mg to 2 g, preferably 0.1 mg to 500 mg and more preferably0.1 mg to 100 mg per day in terms of the total amount of the derivativeof the present invention, and that the blending ratio of the derivativeof the present invention and antioxidant be 0.001 to 1000 parts byweight, preferably 0.01 to 100 parts by weight and more preferably 0.1to 100 parts by weight of antioxidant per 1 part by weight of thederivative of the present invention, since balance modifying effects areenhanced by an antioxidant.

Furthermore, in the case of adding the derivative of the presentinvention to a food raw material that does not substantially contain thederivative of the present invention but contains an antioxidant, andparticularly tocopherols, the derivative of the present invention can beadded so that the content ratio of the derivative of the presentinvention and antioxidant in the finished product is 0.001 to 1000 partsby weight, preferably 0.01 to 100 parts by weight and more preferably0.1 to 100 parts by weight of antioxidant per 1 part by weight of thederivative of the present invention. At this time, antioxidant can befurther added as necessary.

Next, a specific explanation is provided of the present inventionthrough Examples.

EXAMPLES Example 1

Three week old, male Wistar rats (Saitama Laboratory Animal Co., Ltd.)were preliminarily kept for 1 week on solid feed (CE-2, Japan Clea Co.,Ltd.). The animals were divided into six groups of 6 animals each. Theanimals were then raised on standard feed (prepared by Eizai Co., Ltd.)composed of 20% casein, 15% cornstarch, 25% sucrose, 25% glucose, 0.3%DL-methionine, 5% cellulose, 0.2% choline bitartrate, 3.5% mineralmixture, 1% vitamin mixture and 5% prepared lipids. The sesamin addinggroups were given feed in which 0.5% by weight of a purified mixture ofsesamin and episesamin (sesamin: 51.3%, episesamin: 47.8%) was added tothe standard feed. The following indicates the prepared lipids used foreach group along with the addition or non-addition of sesamin.

Group 1: Linoleic acid group

Rapeseed oil:Soybean oil=7:3

(omega-6:omega-3=3:1)

Group 2: Linoleic acid+sesamin group

Rapeseed oil:Soybean oil 7:3

(omega-6:omega-3=3:1)

Group 3: α-Linolenic acid group

Beefsteak plant oil:Safflower oil=7:3

(omega-6:omega-3=1:3)

Group 4: α-Linolenic acid+sesamin group

Beefsteak plant oil:Safflower oil=7:3

(omega-6:omega-3=1:3)

Group 5: Eicosapentaenoic acid (EPA) group

Rapeseed oil:EPA=3:2

Group 6: Eicosapentaenoic acid (EPA)+sesamin group

Rapeseed oil:EPA=3:2

Note that in the EPA group, 5,8,11,14,17-eicosapentaenoic acid ethylester (97%) was used for the EPA, and it was prepared so that it wassubstituted with an amount of EPA nearly equal to the amount ofα-linolenic acid of the α-linolenic acid group. The fatty acidcompositions of the prepared lipids used in each of the groups describedabove are shown in Table 1. The animals were fed for 27 days using thefeed assigned to each group and then sacrificed after 1 day of fastingfollowed by removal of the liver, serum, kidneys, lungs, heart andbrain. After extracting the lipids using the method of Folch, fatty acidmethyl esters were prepared in accordance with routine methods, and thefatty acid compositions were quantified with gas chromatography. Thefatty acid compositions in the liver of each experimental. group areshown in Table 2, while the ratios of omega-6 and omega-3 unsaturatedfatty acids in the liver of each. experimental group are shown in Table3.

                  TABLE 1                                                         ______________________________________                                        Fatty Acid Compositions of Prepared Lipids (%)                                                         18:1   18:2 18:3 20:5                                             16:0 18:0   (n-9)  (n-6)                                                                              (n-3)                                                                              (n-3)                               ______________________________________                                        Linoleic acid group                                                                          5.9    2.3    48.5 31.2 9.9                                    (n-6:n-3  3:1)                                                                Rapeseed oil:Soybean oil =                                                    7:3                                                                           α-linolenic acid group                                                                 6.7    2.1    36.7 14.1 40.3                                   (n-6:n-3 = 1:3)                                                               Beefsteak plant                                                               oil:safflower oil = 7:3                                                       EPA group      2.4    1.0    35.2 13.1 6.5  40.0                              Rapeseed oil:EPA = 3:2                                                        ______________________________________                                         16:0: Palinitic acid                                                          18:0: Stearic acid                                                            18:1 (n9): Oleic acid                                                         18:2 (n6): Linoleic acid                                                      18:3 (n3): Linolenic acid                                                     20:5 (n3): 5,8,11,14, 17eicosapentaenoic acid                                 EPA: 5,8,11,14,17eicosapentaenoic acid ethyl ester (97%)                      (n3): omega3 unsaturated fatty acid                                           (n6): omega6 unsaturated fatty acid                                           (n9): omega9 unsaturated fatty acid                                      

                  TABLE 2                                                         ______________________________________                                        Effects of Sesamin and Ingested Fatty Acids on                                Fatty Acid Composition in the Liver (μmol/g)                               Linoleic acid   α-Linolenic acid                                                                     EPA                                              Sesamin                                                                              -       +        -     +      -     +                                  ______________________________________                                        16:0   21.7 ±                                                                             25.2 ±                                                                              22.5 ±                                                                           29.0 ±                                                                            31.4 ±                                                                           32.3 ±                                 3.42    4.53     2.45  2.03   5.03  4.09                               18:0   17.6 ±                                                                             18.9 ±                                                                              18.2 ±                                                                           22.3 ±                                                                            23.4 ±                                                                           24.3 ±                                 2.67    2.65     2.01  1.57   2.99  2.71                               18:1   19.1 ±                                                                             17.4 ±                                                                              15.1 ±                                                                           15.8 ±                                                                            23.4 ±                                                                           20.3 ±                          (n-9)  4.13    5.83     2.31  2.02   5.22  3.26                               18:2   10.7 ±                                                                             8.36 ±                                                                              14.8 ±                                                                           13.8 ±                                                                            11.1 ±                                                                           11.4 ±                          (n-6)  2.04    1.60     3.50  0.99   1.57  1.02                               18:3   0.83 ±                                                                             0.22 ±                                                                              6.53 ±                                                                           2.25 ±                                                                            1.30 ±                                                                           0.32 ±                          (n-3)  0.21    0.23***  2.16  0.34***                                                                              0.54  0.08***                            20:3   0.55 ±                                                                             1.09 ±                                                                              0.77 ±                                                                           1.60 ±                                                                            0.73 ±                                                                           1.70 ±                          (n-6)  0.11    0.20***  0.06  0.19***                                                                              0.12  0.22***                            20:4   21.1 ±                                                                             24.7 ±                                                                              16.1 ±                                                                           25.6 ±                                                                            9.18 ±                                                                           13.6 ±                          (n-6)  3.39    2.51     2.25  2.05***                                                                              0.76  1.54***                            20:5   0.31 ±                                                                             0.03 ±                                                                              2.40 ±                                                                           0.88 ±                                                                            25.4 ±                                                                           11.5 ±                          (n-3)  0.26    0.06*    0.49  0.08***                                                                              9.15  2.12***                            22:5   0.78 ±                                                                             0.78 ±                                                                              1.73 ±                                                                           2.02 ±                                                                            8.10 ±                                                                           5.96 ±                          (n-3)  0.17    0.33     0.25  0.17   1.60  1.38                               22:6   6.19 ±                                                                             7.14 ±                                                                              6.94 ±                                                                           9.15 ±                                                                            9.29 ±                                                                           7.54 ±                          (n-3)  1.53    0.76     0.93  0.48   1.95  0.88                               Totals 98.9 ±                                                                             103.7 ±                                                                             105.1 ±                                                                          122.6 ±                                                                           143.4 ±                                                                          129.0 ±                                16.0    18.0     14.6  8.57*  25.6  15.2                               ______________________________________                                         Significant difference according to presence or absence of administrated      sesamin among dose groups ingesting the same fatty acid:                      *p < 0.025,                                                                   ***p < 0.005                                                                  16:0 = palmitic acid, 18:0 = stearic acid, 18:1(n9) = oleic acid, 18:2(n6     = linoleic acid, 18:3(n3) = linolenic acid, 20:3(n6) = dihomolinolenic        acid, 20:4(n6) = arachidonic acid, 20:5(n3) = eicosapentaenoic acid,          22:5(n3) = docosapentaenoic acid, 22:6(n3) = docosahexaenoic acid             (n3): omega3 unsaturated fatty acid                                           (n6): omega6 unsaturated fatty acid                                           (n9): omega9 unsaturated fatty acid                                      

                  TABLE 3                                                         ______________________________________                                        Effects of EPA and Sesamin Administration on                                  omega-6/omega-3 Balance in the Liver (μmol/g)                                          omega-6    omega-3                                                            unsaturated                                                                              unsaturated                                                                              omega-6/                                    Sesamin     fatty acids                                                                              fatty acids                                                                              omega-3                                     ______________________________________                                        Linoleic                                                                              -       32.4 ± 5.41                                                                           8.10 ± 1.74                                                                         3.76 ± 0.27                            acid    +       34.1 ± 4.18                                                                           8.15 ± 1.15                                                                         4.20 ± 0.20**                          α-linolenic                                                                     -       31.7 ± 5.65                                                                           17.6 ± 3.23                                                                         1.81 ± 0.16                            acid    +       41.2 ± 2.90***                                                                        14.3 ± 0.88                                                                         2.87 ± 0.13***                         EPA     -       21.1 ± 2.19                                                                           44.1 ± 12.5                                                                         0.50 ± 0.08                                    +       26.7 ± 2.47***                                                                        25.3 ± 4.13***                                                                      1.07 ± 0.11***                         ______________________________________                                         Significant difference between group to which sesamin was added to feed       and group in which it was not added to feed among groups given the same       dietary fatty acids: *p < 0.025, ** p < 0.01, ***p < 0.005               

In the omega-3 unsaturated fatty acid addition group i.e., theα-linolenic acid and EPA group, arachidonic acid content in the liverdecreased and a particularly remarkable decrease was observed in the EPAaddition group. The decrease was significantly improved byadministration of sesamin. Next, the ratios of omega-3 unsaturated fattyacids and omega-6 unsaturated fatty acids in the liver, lung, heart,kidney and brain are shown in FIG. 1. In the linoleic acid group, theratio of omega-6 and omega-3 unsaturated fatty acids is 3:1 which isdesirable for ingested lipids, and the ratio of omega-3 and omega-6unsaturated fatty acids of each tissue in this group was considered tobe at the normal level.

This normal balance was not observed to be affected by administration ofsesamin in any of the tissues. On the other hand, in the α-linolenicacid and EPA group, which is an omega-3 unsaturated fatty acid ingestiongroup, the ratio of omega-6 unsaturated fatty acids decreased in eachtissue, and the decreases were observed to be more remarkable in the EPAgroup in which there is a higher degree of unsaturation. However,sesamin administration caused the ratio of omega-6 unsaturated fattyacids to rise and improve.

The degree of sesamin-induced improvement was demonstrated moreprominently in the EPA group in which was observed a remarkable decreasein the ratio of omega-6 unsaturated fatty acids. Based on the abovefindings, sesamin was clearly shown to modify the balance of fatty acidsto a suitable ratio of omega-6 unsaturated fatty acids and omega-3unsaturated fatty acids in each tissue of the body in order to maintainhomeostasis and prevent disease.

Example 2

Three week old, male Wistar rats (Saitama Laboratory Animal Co., Ltd.)were preliminarily kept for 1 week on solid feed (CE-2, Japan Clea Co.,Ltd.). The animals were divided into seven groups of 6 animals each. Theanimals were then raised on the standard feed used in Example 1. Thesame prepared lipids used for the linoleic acid group in Example 1 inwhich rapeseed oil:soybean oil=7:3 were used for Group 1. The sameprepared lipids as the EPA group in Example 1 were used for theremaining six groups (rapeseed oil:EPA=3:2). For thedioxabicyclo(3.3.0)octane derivatives, sesaminol (Compound A) purifiedfrom refined sesame oil, sesamolin (Compound B), prepared from crudesesame oil,2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane(Compound C),2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane(Compound D) and2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo(3.3.0)octane(Compound E) prepared from an extract of sesame seeds were used byadding 0.5% by weight after preparing in accordance with a previouslyfiled patent (Japanese Patent Application No. 63-53642). The followingindicates the prepared lipids used for each group along with thedioxabicyclo(3.3.0)octane derivative that was added.

Group 1: Linoleic acid group

Rapeseed oil:Soybean oil=7:3

(omega-6:omega-3=3:1)

Group 2: EPA group

Rapeseed oil:EPA=3:2

Group 3: EPA+Compound A Group

Rapeseed oil:EPA=3:2

Group 4: EPA+Compound B Group

Rapeseed oil:EPA=3:2

Group 5: EPA+Compound C Group

Rapeseed oil:EPA=3:2

Group 6: EPA+Compound D Group

Rapeseed oil:EPA=3:2

Group 7: EPA+Compound E Group

Rapeseed oil:EPA=3:2

The animals were fed for 27 days using the feed assigned to each groupand then sacrificed after 1 day of fasting followed by removal of theliver. After extracting the lipids using the method of Folch, fatty acidmethyl esters were prepared in accordance with routine methods, and thefatty acid compositions were quantified with gas chromatography. Thearachidonic acid contents in the liver of Groups 1 through 7 were21.1±3.39, 9.18±0.76, 12.8±1.10, 11.8±0.98, 10.9±1.07, 12.1±1.20 and11.5±0.49 (μmol/g), respectively.

Although a remarkable decrease in arachidonic acid content in the liverwas observed due to ingestion of EPA, this was significantly improved byadministration of dioxabicyclo(3.3.0)octane derivative. As has beendescribed above, dioxabicyclo(3.3.0)octane derivative was clearly shownto modify the balance of fatty acids to a suitable ratio of omega-6unsaturated fatty acids and omega-3 unsaturated fatty acids in eachtissue of the body in order to maintain homeostasis and prevent disease.

Example 3

Rats were fed using the same materials and procedure as Example 1 withthe exception of the prepared lipids. The following indicates theprepared lipids used for each group along with the addition ornon-addition of sesamin.

Group 1: Linoleic acid group

Soybean oil:Beefsteak plant oil=5:1

(omega-6:omega-3=2.7:1)

Group 2: Linoleic acid+sesamin group

Soybean oil:Beefsteak plant oil=5:1

(omega-6:omega-3=2.7:1)

Group 3: Arachidonic acid group

Beefsteak plant oil:Palm oil:AA=2:1:2

(omega-6:omega-3=3.6:1)

Group 4: Arachidonic acid+sesamin group

Beefsteak plant oil:Palm oil:AA=2:1:2

(omega-6:omega-3=3.6:1)

Note that in arachidonic acid groups, arachidonic ethyl ester (99%) wasused for the AA, the total amount of omega-6 unsaturated fatty acids wasmade to be equal to that of the arachidonic acid group and linoleic acidgroup, and the arachidonic acid group was prepared so that the majorityof linoleic acid in the linoleic acid groups was substituted witharachidonic acid. The fatty acid compositions of the prepared lipidsused in each of the groups described above are shown in Table 4.

                  TABLE 4                                                         ______________________________________                                        Fatty Acid Compositions of Prepared Lipids (%)                                                         18:1   18:2 18:3 20:4                                             16:0 18:0   (n-9)  (n-6)                                                                              (n-3)                                                                              (n-6)                               ______________________________________                                        Linoleic acid group                                                                          9.53   3.44   22.55                                                                              46.25                                                                              17.21                                                                              0                                 (n-6:n-3 = 2.7:1)                                                             Soybean oil:Beefsteak                                                         plant oil = 5:1                                                               Arachidonic acid group                                                                       18.82  2.12   18.54                                                                              6.66 12.88                                                                              40.0                              (n-6:n-3 = 3.6:1)                                                             Beefsteak plant oil:palm                                                      oil:AA = 2:1:2                                                                ______________________________________                                         AA: Arachidonic acid ethyl ester (99%)                                   

The animals were fed for 27 days using the feed assigned to each groupand then sacrificed after 1 day of fasting followed by removal of theliver, serum, kidneys, lungs, heart and brain. After extracting thelipids using the method of Folch, fatty acid methyl esters were preparedin accordance with routine methods, and the fatty acid compositions werequantified with gas chromatography. The fatty acid compositions in theliver of each experimental group are shown in Table 5, while the ratiosof omega-6 and omega-3 unsaturated fatty acids in the liver of eachexperimental group are shown in Table 6.

                  TABLE 5                                                         ______________________________________                                        Effects of Sesamin and Ingested Fatty Acids on                                Fatty Acid Composition in the Liver (μmol/g tissue)                        Sesa-                                                                              Linoleic acid    Arachidonic acid                                        min  -         +          -        +                                          ______________________________________                                        18:0 25.9 ± 4.90                                                                          24.0 ± 2.09                                                                           23.6 ± 2.86                                                                         22.2 ± 0.73                             18:1 26.4 ± 6.78                                                                          17.0 ± 5.17                                                                           17.2 ± 4.32*                                                                        13.1 ± 0.87***                          (n-9)                                                                         18:2 28.3 ± 7.27                                                                          15.9 ± 2.16**                                                                         3.85 ± 0.64***                                                                      2.99 ± 0.24***                          (n-6)                                                                         18:3 0.53 ± 0.17                                                                          0.16 ± 0.04***                                                                        0.45 ± 0.11                                                                         0.10 ± 0.03***c                         (n-6)                                                                         18:3 4.02 ± 1.29                                                                          0.92 ± 0.20***                                                                        2.82 ± 0.73                                                                         0.55 ± 0.08***c                         (n-3)                                                                         20:3 0.69 ± 0.14                                                                          1.20 ± 0.27***                                                                        0.61 ± 0.17                                                                         0.42 ± 0.10***                          (n-6)                                                                         20:4 29.8 ± 5.05                                                                          32.5 ± 3.16                                                                           71.7 ± 14.0***                                                                      42.2 ± 1.64***c                         (n-6)                                                                         20:5 0.84 ± 0.17                                                                          0.20 ± 0.05***                                                                        0.47 ± 0.19**                                                                       0.03 ± 0.03***c                         (n-3)                                                                         22:5 1.60 ± 0.19                                                                          1.45 ± 0.20                                                                           2.00 ± 0.50                                                                         1.83 ± 0.48                             (n-3)                                                                         22:6 9.13 ± 1.27                                                                          9.08 ± 1.14                                                                           5.50 ± 1.16***                                                                      5.68 ± 1.12***                          (n-3)                                                                         ______________________________________                                         Significant difference relative to linoleic acid group: *p < 0.025, **p <     0.01, ***p < 0.005                                                            Significant difference between arachidonic acid group and arachidonic aci     + sesamin group: c: p < 0.005                                            

                  TABLE 6                                                         ______________________________________                                        Effects of AA and Sesamin Administration on                                   omega-6/omega-3 Balance in the Liver (μmol/g tissue)                                  omega-6   omega-3                                                  Sesa-      unsaturated                                                                             unsaturated                                              min        fatty acids                                                                             fatty acids omega-6/omega-3                              ______________________________________                                        Linoleic                                                                              -      59.7 ± 12.0                                                                          15.8 ± 1.79                                                                          3.78 ± 0.61                             acid    +      50.1 ± 5.24                                                                          11.8 ± 1.45***                                                                       4.27 ± 0.33                             Arachidonic                                                                           -      82.0 ± 16.1*                                                                         11.0 ± 2.18***                                                                       7.58 ± 1.09***                          acid    +      47.6 ± 1.83.sup.f                                                                    8.24 ± 1.52***.sup.c,d                                                               5.95 ± 1.24***.sup.b                    ______________________________________                                         Significant difference relative to linoleic acid group: ***p < 0.005          Significant difference between linoleic acid + sesamin group and              arachidonic acid + sesainin group: .sup.b p < 0.01, .sup.c p < 0.005          Significant difference between arachidonic acid group and arachidonic aci     + sesamin group: .sup.d p < 0.025, .sup.f p < 0.005                      

The ingested amount of linoleic acid is preferably such that the ratioof omega-6 and omega-3 unsaturated fatty acids is 2.7:1 as ingestedlipids. The ratio of omega-3 and omega-6 unsaturated fatty acids in eachtissue of this group is considered to be at the normal level. On theother hand, in the arachidonic acid group, although it is desirable toingest this fatty acid so that the ratio of omega-6 and omega-3unsaturated fatty acids is 3.6:1 as ingested lipids, due to excessiveingestion of arachidonic acid, the content of arachidonic acid in theliver increased remarkably and an increase was also observed in theamount of omega-6 unsaturated fatty acids. This condition wassignificantly improved by administration of sesamin, however. Next, FIG.2 indicates the ratios of omega-3 unsaturated fatty acids and omega-6unsaturated fatty acids in the liver, lung, heart, kidney and brain.

Example 4

2.4 g of the mixture of the derivative of the present invention used inExample 1 was added to 100 g of butterfat from which the buttermilk hadbeen removed in the churning procedure of the butter production process.This was followed by working to form a homogeneous composition andobtain butter having the action of modifying the balance of omega-6 andomega-3 unsaturated fatty acids.

Example 5

0.5 g of the derivative of the present invention was mixed with 20.5 gof silicic anhydride followed by the addition of 79 g of cornstarch andfurther mixing. 100 ml of a 10% hydroxypropylcellulose-ethanol solutionwere added to this compound followed by kneading, extrusion and dryingin accordance with routine methods to obtain granules.

Example 6

7 g of the mixture of the derivative of the present invention used inExample 1 was mixed with 20 g of silicic anhydride followed by theaddition of 10 g of microcrystalline cellulose, 3 g of magnesiumstearate and 60 g of lactose and mixing. This mixture was then formedinto tablets using a single-action tablet making machine to producetablets having a diameter of 7 mm and weighing 100 mg.

Example 7

2.5 g of the derivative of the present invention was heated anddissolved in 200 g of TO-10M (Nikko Chemicals), a non-ionic surfaceactivator, followed by the addition of 4.7975 liters of sterilephysiological saline heated to 60° C. After stirring well, the solutionwas antiseptically filled into vials and sealed to produce injectionpreparations.

Example 8

Water was added to 100 parts by weight of gelatin and 35 parts by weightof food-additive glycerin, and the mixture was melted at 50-60° C. toprepare a gelatin coating having a viscosity of 20,000 cps. Next, 95.1%wheat germ oil, 2.9% vitamin E oil and 2% of the mixture of thederivative of the present invention used in Example 1 were mixed toprepare the contents for the above-mentioned gelatin coating. Using thecoating and its contents, capsules were formed and dried in accordancewith routine methods to produce soft capsules containing 180 mg of theabove-mentioned contents per capsule. Each said capsule contained 3.6 mgof the mixture of the derivative of the present invention and 2.34 mg ofα-tocopherol.

Example 9

1 g of tuna oil (arachidonic acid=2.1%, eicosapentaenoic acid=3.6%,docosahexaenoic acid=15.6%) and 100 mg of the mixture of the derivativeof the present invention used in Example 1 were blended with 100 g ofpowdered milk raw material to produce powdered milk in accordance withroutine methods. As a result, a prepared powdered milk was obtained thatcontained omega-6/omega-3 unsaturated fatty acid balance modifier.

INDUSTRIAL APPLICABILITY

The omega-3/omega-6 unsaturated fatty acid balance modifier of thepresent invention is effective in maintaining homeostasis in the bodyand preventing disease since it is able to easily regulate the balanceof omega-3 unsaturated fatty acids and omega-6 unsaturated fatty acidsto an ideal value without placing any particular restrictions on dietarycontent. In addition, it is also superior in terms of its safety and canbe used in various foods.

I claim:
 1. A method for modifying the balance of omega-6 and omega-3unsaturated fatty acids comprising administrating adioxabicyclo(3.3.0)octane derivative having a formula (I): ##STR4##wherein, R¹, R², R³, R⁴, R⁵ and R⁶ are respectively and independently ahydrogen atom or alkyl group having 1-3 carbon atoms, or R¹ and R²and/or R⁴ and R⁵ together represent a methylene group or ethylene group,and n, m and l represent 0 or
 1. 2. A method as set forth in claim 1wherein said dioxabicyclo(3.3.0)octane derivative is at least one of thecompounds selected from sesamin, sesaminol, episesamin, episesaminol,sesamolin,2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0)octane,2,6-bis-(3-methoxy-4-hydroxyphenyl)-3,7-dioxabicyclo(3.3.0) octane, and2-(3,4-methylenedioxyphenyl)-6-(3-methoxy-4-hydroxyphenoxy)-3,7-dioxabicyclo(3.3.0)octane.3. A method as set forth in claim 1 wherein said omega-3 unsaturatedfatty acid is at least one of 9,12,15-octadecatrienoic acid (α-linolenicacid), 6,9,12,15-octadecatetraenoic acid, 8,11,14,17-eicosatetraenoicacid, 5,8,11,14,17-eicosapentaenoic acid, 7,10,13,16,19-docosapentaenoicacid and 4,7,10,13,16,19-docosahexaenoic acid.
 4. A method as set forthin claim 1 wherein said omega-6 unsaturated fatty acid is at least oneof 9,12-octadecadienoic acid (linoleic acid), 6,9,12-octadecatrienoicacid (γ-linolenic acid), 8,11,14-eicosatrienoic acid (dihomo-γ-linolenicacid) and 5,8,11,14-eicosatetraenoic acid (arachidonic acid).
 5. Amethod as set forth in claim 1 comprising administering an antioxidanttogether with said dioxabicyclo(3.3.0)octane derivative.
 6. A method asset forth in claim 5 wherein said antioxidant is a tocopherol.